Rheumatoid arthritis is a seroius health problem of unknown etiology for which there exist two experimental autoimmune models: adjuvant arthritis (AA) and collagen type II arthritis (CA). AA can be induced in susceptible strains of rats by immunizing them against a suspension of Mycobacteria in oil called complete Freund's adjuvant (CFA). CA can be induced in either rats of mice by immunizing them against collagen type II, the characteristic collagen of joints. The laboratory of the Principal Investigator has developed lines of T lymphocytes from rats with AA or CA. Some of these lines can mediate arthritis upon intravenous inoculation into naive rats and, thus, function as etiologic agents of autoimmune arthritis. However, these and other lines may also be used to vaccinate rats against the subsequent induction of active arthritis by immunization with CFA. The aims of this proposal are to exploit these T cell lines to learn how the immune system causes arthritis and how vaccination against arthritis may be achieved. Specifically, we shall select clones from the lines and characterize their function as agents of disease or protection; analyze antigenic fine specificity and cross-reactivity between collagen II and bacterial antigens; identify genetic and cellular aspects of cells mediating disease and/or protection; isolate subcellular materials capable of vaccinating against arthritis; and investigate the possibility of treating active, ongoing arthritis using specific line cells and their products. The results of these studies could have important implications for our understanding and control of human autoimmune diseases such as rheumatoid arthritis.